title: Association of common gene variants in the WNT/β-catenin pathway with colon cancer recurrence.
abstract: Wnt/β-catenin signaling has a central role in the development and progression of most colon cancers (CCs). Germline variants in Wnt/β-catenin pathway genes may result in altered gene function and/or activity, thereby causing inter-individual differences in relation to tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of Wnt/β-catenin pathway genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II CC. A total of 234 patients treated with 5-fluorouracil-based chemotherapy were included in this study. Whole-blood samples were analyzed for putative functional germline polymorphisms in SFRP3, SFRP4, DKK2, DKK3, Axin2, APC, TCF7L2, WNT5B, CXXC4, NOTCH2 and GLI1 genes by PCR-based restriction fragment-length polymorphism or direct DNA sequencing. Polymorphisms with statistical significance were validated in an independent study cohort. The minor allele of WNT5B rs2010851 T>G was significantly associated with a shorter TTR (10.7 vs 4.9 years; hazard ratio: 2.48; 95% CI, 0.96-6.38; P=0.04) in high-risk stage II CC patients. This result remained significant in multivariate Cox's regression analysis. This study shows that the WNT5B germline variant rs2010851 was significantly identified as a stage-dependent prognostic marker for CC patients after 5-fluorouracil-based adjuvant therapy.
authors.affiliation: 1] Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA [2] Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Páez
authors.affiliation: 1] Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA [2] Division of Clinical Oncology, Research Unit Genetic Epidemiology and Pharmacogenetics, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Gerger
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.affiliation: 1] Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA [2] Department of Biology and Chemistry, Azusa Pacific University, Azusa, CA, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Labonte
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Benhanim
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kahn
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Lenz
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Lenz
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ning
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Wakatsuki
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Loupakis
authors.affiliation: 1] Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA [2] University of Southern California, Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D051153:Wnt Proteins / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics*
chemical_list: C435831:WNT5B protein, human; D051153:Wnt Proteins; D005472:Fluorouracil